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Beatriz Padrela¹, Mervin Tee², Markus Sneve³, Amnah Mahroo⁴, Oliver Geier⁵, David Thomas⁶, Catherine Morgan⁷, Paulien Moyaert^8,9, Esin Ozturk¹⁰, Wibeke Nordhøy¹¹, Lene Pålhaugen¹², Jennifer Linn¹³, Per Selnes¹², Klaus Eickel^4,14, Simon Konstandin^4,14, Joost Kuijer¹, Daniel Hoinkiss⁴, Nora Breutigam⁴, Mareike Buck⁴, Rik Achten⁹, Frederik Barkhof^1,15, Saima Hilal², Tormod Fladby^12,16, Udunna Anazodo⁸, Jan Petr¹⁷, Henk J.M.M. Mutsaerts¹, and Matthias Günther^4
1Department of Radiology and Nuclear Medicine, Amsterdam UMC, Amsterdam, Netherlands, ²National University of Singapore and National University Health System, Saw Swee Hock School of Public Health, Singapore, Singapore, ³Department of Psychology, University of Oslo, Center for Lifespan Changes in Brain and Cognition, Oslo, Norway, ⁴Fraunhofer-Insitute for Digital Medicine MEVIS,, Bremen, Germany, ⁵Clinics of Radiology and Nuclear Medicine, University of Oslo, Department of Physics and Computational Radiology, Oslo, Norway, ⁶University College London, Dementia Research Center, London, United Kingdom, ⁷University of Auckland, School of Psychology and Centre for Brain Research, Auckland, New Zealand, ⁸Lawson Health Research Institute, London, ON, Canada, ⁹Department of Medical Imaging, Ghent University Hospital, Gent, Belgium, ¹⁰Bogazici University, Institute of Biomedical Engineering, Istanbul, Turkey, ¹¹Clinics of Radiology and Nuclear Medicine, Oslo University Hospital, Department of Physics and Computational Radiology, Oslo, Norway, ¹²Department of Neurology, Akershus University Hospital, Lørenskog, Norway, ¹³Technische Universität Dresden, Department of Neuroradiology, University Hospital Carl Gustav Carus, Dresden, Germany, ¹⁴mediri GmbH, Heidelberg, Germany, ¹⁵University College London, Queen Square Institute of Neurology and Centre for Medical Image Computing (CMIC), London, United Kingdom, ¹⁶University of Oslo, Institute of Clinical Medicine, Campus Ahus, Lørenskog, Norway, ¹⁷Institute of Radiopharmaceutical Cancer Research, Helmholtz-Zentrum Dresden-Rossendorf, Dresden, Germany

Keywords: Alzheimer's Disease, Aging

One of the earliest signs of Alzheimer’s disease (AD) is the loss of blood-brain barrier (BBB) integrity. Arterial spin labeling (ASL) MRI is a non-invasive way to measure perfusion and several other hemodynamic and physiological parameters, including vascular permeability. The DEveloping BBB-ASL as non-Invasive Early biomarker (DEBBIE) consortium aims to develop and integrate innovative techniques to allow robust BBB permeability assessments by ASL to develop a sensitive, non-invasive, and early biomarker for AD and related dementias. This work summarizes our planned efforts to develop and establish an MRI-based BBB permeability biomarker.

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Zhiliang Wei^1,2, Hongshuai Liu³, Zixuan Lin¹, Minmin Yao³, Ruoxuan Li³, Chang Liu³, Yuguo Li^1,2, Jiadi Xu^1,2, Wenzhen Duan^3,4, and Hanzhang Lu^1,2,5
1Russell H. Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ²F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Research Institute, Baltimore, MD, United States, ³Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ⁴The Solomon H. Snyder Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD, United States, ⁵Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, United States

Keywords: Arterial spin labelling, Animals

Blood-brain barrier (BBB) plays a critical role in brain health and diseases. However, there is a scarcity of tools to assess BBB integrity, particularly in mouse models. Here, we aimed to develop a non-contrast arterial-spin-labeling-based MRI technique to estimate BBB permeability in mice by measuring relative fractions of labeled water in cerebral veins. Systematic optimizations were performed to enhance signal sensitivity with a further study investigating reproducibility. The proposed method revealed significant BBB dysfunctions in a mouse model of Huntington’s disease, which were further validated with histology. Our method may open new avenues for preclinical mechanistic research or therapeutic trails.

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Yolanda Ohene^1,2, Will Harris ³, Elizabeth Powell⁴, Nina W. Wycech³, Samo Lasič^5,6, Kieron South³, Graham Coutts³, Andrew Sharp⁷, Catherine B. Lawrence ³, Hervé Boutin ³, Geoff J. M. Parker^4,8, Laura M. Parkes^1,2, and Ben R. Dickie^2,9
1Division of Psychology, Communication and Human Neuroscience, University of Manchester, Manchester, United Kingdom, ²Geoffrey Jefferson Brain Research Centre, University of Manchester, Manchester, United Kingdom, ³Division of Neuroscience, University of Manchester, Manchester, United Kingdom, ⁴UCL, London, United Kingdom, ⁵Danish Research Centre for Magnetic Resonance, Copenhagen, Denmark, ⁶Random Walk Imaging, Åkarp, Sweden, ⁷Evotec (UK) Ltd., Cheshire, United Kingdom, ⁸Bioxydyn Limited, Manchester, United Kingdom, ⁹Division of Informatics, University of Manchester, Manchester, United Kingdom

Keywords: Diffusion/other diffusion imaging techniques, Permeability

Non-disruption alterations to the blood-brain barrier (BBB) can be difficult to detect and therefore require highly sensitive tools for reliable measurement. Here, we apply a BBB filter exchange imaging (BBB-FEXI) technique to assess the rat brain in response to mild Streptococcus pneumoniae lung infection. We observe a significant 78 ± 39 % increase in BBB water permeability during infection. Higher water exchange measures were associated with higher levels of vascular inflammation, while BBB tight junction proteins remained unchanged. The expression of aquaporin-4 water channel was 38% higher in infected animals, which may drive the increase in water exchange during infection.

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Keywords: Arterial spin labelling, Neurofluids

The recent years have seen a growing interest in the study of brain waste clearance mechanisms, also referred to as glymphatics. Recently, ASL has been used to image choroid plexus perfusion but also the exchange between blood and CSF by taking advantage of the long CSF T2 compared to blood and brain tissue. We evaluate the possibility to measure this using reduced flip-angles FSE with variable-density k-space sampling, using a split echo-train strategy to collect in the same echo-train a short-TE PD-weighted as well as long-TE T2-weighted ASL datasets. We evaluate in a pilot group potential age-related differences.

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Joseph G. Woods¹, Mark Chiew^1,2,3, and Thomas W. Okell^1
1Wellcome Centre for Integrated Neuroimaging, FMRIB, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford, United Kingdom, ²Department of Medical Biophysics, University of Toronto, Toronto, ON, Canada, ³Physical Sciences, Sunnybrook Research Institute, Toronto, ON, Canada

Keywords: Arterial spin labelling, High-Field MRI

Interest in 7T PCASL is increasing due to the large potential increases in SNR. However, PCASL is a relatively high SAR technique, requiring TRs to be extended with deadtime at 7T,  which reduces SNR-efficiency and some of the benefit of moving to 7T. Here, we demonstrate that using VERSE to reduce the SAR of both the PCASL and background suppression pulses can reduce TRs by almost 25%, leading to an improvement in tSNR-efficiency compared to an equivalent non-VERSE scan. We reduced the off-resonance sensitivity that VERSE introduces to the background suppression pulses by carefully optimizing the phase waveform.
 

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Didi Chi^1,2, Yasmin Blunck^1,2, Rebecca Glarin², Catherine E. Davey^1,2, Daniel Stäb³, Josef Pfeuffer⁴, Leigh A. Johnston^1,2, and Jin Jin^5
1Department of Biomedical Engineering, University of Melbourne, Parkville, Australia, ²Melbourne Brain Centre Imaging Unit, University of Melbourne, Parkville, Australia, ³MR Research Collaborations, Siemens Healthcare Pty Ltd, Melbourne, Australia, ⁴MR Research Collaborations, Siemens Healthcare Pty Ltd, Sydney, Australia, ⁵MR Research Collaborations, Siemens Healthcare Pty Ltd, Brisbane, Australia

Keywords: Arterial spin labelling, Arterial spin labelling, Pulsed ASL

The increased power deposition and inhomogeneity of $$$\Delta{B_0}$$$ and $$$B_1^+$$$ fields limit the application of ASL at 7T. A new type of asymmetric adiabatic pulses, Hybrid Adiabatic Pulses with asYmmetry (HAPY) along with its optimisation scheme, is proposed in this study. In simulation and phantom experiments, the proposed HAPY pulse demonstrates RF labelling pulse energy reduction and high labelling efficiency under challenging $$$\Delta{B_0}$$$ and $$$B_1^+$$$ conditions. In vivo experiments show the successful application of PICORE-PASL with HAPY labelling pulses in 7T ASL with increased temporal resolution.

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Paul Han^1,2, Thibault Marin^1,2, Yue Zhuo^1,2, Jinsong Ouyang^1,2, Georges El Fakhri^1,2, and Chao Ma^1,2
1Gordon Center for Medical Imaging, Department of Radiology, Massachusetts General Hospital, Boston, MA, United States, ²Department of Radiology, Harvard Medical School, Boston, MA, United States

Keywords: Arterial spin labelling, Perfusion, Brain

Arterial spin labeling (ASL) is a non-invasive MRI technique that allows to quantitatively measure cerebral blood flow. However, the major limitation of ASL is in the intrinsically low signal-to-noise ratio (SNR). Balanced steady-state free precession (bSSFP) sequence has been proposed to mitigate this limitation, however, bSSFP is sensitive to off-resonance effects. ASL perfusion imaging with bSSFP can be sensitive to effects from motion and flow when Cartesian sampling scheme is used. This work proposes and investigates radial sampling scheme for ASL with bSSFP to allow perfusion imaging with relatively high SNR and robustness to motion and off-resonance effects. 

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Keywords: Arterial spin labelling, Perfusion

In this study, a framework was set up for the simultaneous acquisition of 4D MRA and perfusion ASL data while maintaining whole brain coverage. A Hadamard-8 preparation was combined with a 3D Stack of Spirals readout which resulted in 7 timepoints. By combining these two techniques we were able to obtain both angiography and perfusion from a single dataset. By improving the efficiency of the sampling scheme i.e. using variable density spirals, the total scan time could be reduced further while improving the SNR during the perfusion phase, albeit at the expense of the quality of the 4D MRA.

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Ian D Driver¹, Hannah L Chandler¹, Eleonora Patitucci², Richard G Wise^1,3,4, and Michael Germuska^2
1Cardiff University Brain Research Imaging Centre (CUBRIC), School of Psychology, Cardiff University, Cardiff, United Kingdom, ²Cardiff University Brain Research Imaging Centre (CUBRIC), School of Physics and Astronomy, Cardiff University, Cardiff, United Kingdom, ³Department of Neurosciences, Imaging and Clinical Sciences, ‘G. d’Annunzio University’ of Chieti-Pescara, Chieti, Italy, ⁴Institute for Advanced Biomedical Technologies (ITAB), ‘G. d’Annunzio University’ of Chieti-Pescara, Chieti, Italy

Keywords: Arterial spin labelling, Brain, cerebrovascular reactivity

Velocity-selective ASL (VSASL) measurement of CBF is relatively insensitive to arterial arrival times, unlike other ASL techniques, making it suitable for measuring CBF in patient groups with long arrival times. However, VSASL can underestimate CBF when the trailing edge of the labelled bolus arrives before imaging. Our study finds substantial spatial heterogeneity in bolus duration in Fourier Transform velocity-selective inversion (FT-VSI), with short bolus durations in anterior regions and longer bolus durations in posterior regions. These results build on a recent VSASL consensus paper contributing to recommendations for cerebrovascular reactivity mapping experiments.

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Mareike Alicja Buck^1,2, Klaus Eickel^1,3, and Matthias Günther^1,2,3
1Fraunhofer MEVIS, Bremen, Germany, ²University Bremen, Bremen, Germany, ³mediri GmbH, Heidelberg, Germany

Keywords: Arterial spin labelling, Arterial spin labelling, velocity-selective Arterial Spin Labeling, multi-TE

In this work, for the first time, an analytical model for determining the exchange times for obtaining vascular permeability information in velocity-selective Arterial Spin Labeling (VSASL) with multiple echo times (TE) is presented. Signal intensity comparisons were performed between different multi-TE VSASL techniques with each of the standard multi-TE pCASL and multi-TE PASL techniques for different sampling times. This demonstrates that, particularly for longer arterial transit times, the VSASL signal is twice as high compared with standard multi-TE measurements and thus shows promise in the field of non-invasive permeability measurements.

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Linh N. N. Le¹, Gregory J. Wheeler¹, Evan Fletcher², Nicholas P. Blockley³, and Audrey P. Fan^1,2
1Department of Biomedical Engineering, University of California, Davis, Davis, CA, United States, ²Department of Neurology, University of California, Davis, Davis, CA, United States, ³School of Medicine & Health Sciences, University of Nottingham, Nottingham, United Kingdom

Keywords: Oxygenation, Aging

Oxygen Extraction Fraction (OEF) is a valuable indicator of brain physiology influenced by cognitive impairment and vascular pathology in older adults. Our objective is to explore age-related OEF change for cognitively normal (CN) and Mild-Cognitive-Impairment (MCI) subjects. In this study, 56 elderly participants were recruited. Individuals with MCI resulted in higher OEF compared to CN participants, especially in the occipital lobe (p=0.007). In parietal lobe, we observed an inverse correlation between OEF and age (p=0.026) in CN and positive association between OEF and executive function (p=0.023) in MCI. The results showed an effect of aging and cognitive impairment on OEF

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Gabriel Hoffmann^1,2, Franziska Richter¹, Jan Kufer¹, Lena Schmitzer¹, Carina Gleißner¹, Jens Göttler¹, Stephan Kaczmarz^1,2,3, and Christine Preibisch^1,2
1Department of Diagnostic and Interventional Neuroradiology, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany, ²TUM-Neuroimaging Center, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany, ³Philips GmbH Market DACH, Hamburg, Germany

Keywords: Multi-Contrast, Validation, Cerebrovascular reactivity

Combined measurement of BOLD- and CBF-based CVR by means of deASL would be valuable for assessment of cerebrovascular diseases. To investigate the applicability of deASL for CVR mapping, we acquired GE-EPI, deASL and pCASL data from 21 healthy volunteers during a hypercapnia challenge. BOLD-CVR from deASL was slightly but significantly less sensitive to hypercapnia-induced BOLD signal changes than GE-EPI, while differences between deASL- and pCASL-based CBF-CVR were rather insignificant. However, deASL failed in 5 of 21 subjects, while pCASL and GE-EPI merely failed in two and one subjects, respectively. Thus, we expect an elevated deASL failure rate in patient populations.

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THI THUY LE^1,2,3, GEUN HO IM¹, CHAN HEE LEE¹, and SEONG-GI KIM^1,2,3
1Center for Neuroscience Imaging Research (CNIR), Institute for Basic Science (IBS), Suwon, 16419, Republic of Korea, Suwon, Korea, Republic of, ²Department of Biomedical Engineering, Sungkyunkwan University, Suwon, 16419, Republic of Korea, Suwon, Korea, Republic of, ³Department of Intelligent Precision Healthcare Convergence, Sungkyunkwan University, Suwon, 16419, Republic of Korea, Suwon, Korea, Republic of

Keywords: Hematologic, DSC & DCE Perfusion

Transient hypoxia-induced BOLD-DSC perfusion imaging approach can noninvasively map cerebral blood flow (CBF) and cerebral blood volume (CBV) in animals with injectable anesthetics. Since animal models are frequently investigated in translational research under volatile anesthetics, we developed a simple gas delivery system for inducing transient hypoxia, and performed perfusion studies of mouse under isoflurane and dexmedetomidine. Highly sensitive and reproducible perfusion metrics were found, and regional impact of anesthesia to basal perfusion metrics was assessed.

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Thomas W Okell¹, Karla L Miller¹, Martin Craig², Fidel Alfaro-Almagro¹, David L Thomas^3,4, Enrico De Vita⁵, Matthias Günther⁶, Paul M Matthews⁷, Stephen M Smith¹, and Michael A Chapell^2
1Wellcome Centre for Integrative Neuroimaging, FMRIB, Nuffield Department of Clinical Neurosciences, University of Oxford, Oxford, United Kingdom, ²Sir Peter Mansfield Imaging Centre, School of Medicine, University of Nottingham, Nottingham, United Kingdom, ³Dementia Research Centre, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom, ⁴Dept of Brain Repair and Rehabilitation, UCL Queen Square Institute of Neurology, University College London, London, United Kingdom, ⁵MR Physics group, Radiology Department, Great Ormond Street Hospital, London, United Kingdom, ⁶Fraunhofer Institute for Digital Medicine MEVIS, Bremen, Germany, ⁷Department of Brain Sciences, Imperial College London, London, United Kingdom

Keywords: Arterial spin labelling, Arterial spin labelling

UK Biobank is an ongoing study which will acquire brain imaging in 100,000 participants, along with detailed lifestyle, biochemical and genetic information, and long-term health records. Here we describe the recent addition of arterial spin labeling (ASL) perfusion imaging to UK Biobank, with preliminary analyses of the first ~3,500 subjects. These revealed a range of highly significant associations between ASL metrics and non-imaging measures (e.g., blood pressure), as well as other imaging measures (e.g., white matter hyperintensity volume). This should become a useful resource for studying perfusion differences across a population and prior to disease onset.